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The CB1/CB2 receptor agonist WIN-55,212-2 reduces viability of human Kaposi's sarcoma cells in vitro.

Abstract

Kaposi's sarcoma is a highly vascularized mesenchymal neoplasm arising with multiple lesions of the skin. Endogenous cannabinoids have been shown to inhibit proliferation of a wide spectrum of tumor cells. We studied the effects of cannabinoids on human Kaposi's sarcoma cell proliferation in vitro. To do so, we first investigated the presence of the cannabinoid receptors CB(1) and CB(2) mRNAs in the human Kaposi's sarcoma cell line KS-IMM by RT-PCR and, subsequently, the effects of the mixed CB(1)/CB(2) agonist WIN-55,212-2 (WIN) on cell proliferation in vitro. WIN showed antimitogenic effects on Kaposi's sarcoma cells. Western blot analysis of Kaposi's sarcoma lysates suggested that WIN treatment induced activation of both caspase-3 and -6, as well as increased phosphorylation of the stress kinase p38 and JNK, along with transient phosphorylation of ERK(1/2). To better characterize the involvement of each single CB receptor in cannabinoid-induced cell death, we incubated Kaposi's sarcoma cells with different selective cannabinoid receptor agonists, respectively ACEA (CB(1)) and JWH-133 (CB(2)). None of the agonists was able to induce KS-IMM cell apoptosis. Moreover, we co-incubated Kaposi's sarcoma cells with WIN-55,212-2 and either the CB(1) receptor antagonist AM251, the CB(2) receptor antagonist AM630, or a combination of both substances. The CB(2) receptor antagonist AM630 was able to significantly increase survival of Kaposi's sarcoma cells treated with WIN. In view of the antiproliferative effects of cannabinoids on KS-IMM cells, one could envision the cannabinoid system as a potential target for pharmacological treatment of Kaposi's sarcoma.

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  • Authors+Show Affiliations

    ,

    Department of Experimental and Clinical Pharmacology, University of Catania School of Medicine, 95125 Catania, Italy.

    , , , , ,

    Source

    European journal of pharmacology 616:1-3 2009 Aug 15 pg 16-21

    MeSH

    Animals
    Antineoplastic Agents
    Benzoxazines
    Cannabinoids
    Caspases
    Cell Line, Tumor
    Cell Proliferation
    Cell Survival
    Enzyme Activation
    Female
    Gene Expression Regulation, Neoplastic
    Humans
    Mitogen-Activated Protein Kinases
    Morpholines
    Naphthalenes
    Pregnancy
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Sarcoma, Kaposi
    Substrate Specificity

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19539619

    Citation

    Luca, Tonia, et al. "The CB1/CB2 Receptor Agonist WIN-55,212-2 Reduces Viability of Human Kaposi's Sarcoma Cells in Vitro." European Journal of Pharmacology, vol. 616, no. 1-3, 2009, pp. 16-21.
    Luca T, Di Benedetto G, Scuderi MR, et al. The CB1/CB2 receptor agonist WIN-55,212-2 reduces viability of human Kaposi's sarcoma cells in vitro. Eur J Pharmacol. 2009;616(1-3):16-21.
    Luca, T., Di Benedetto, G., Scuderi, M. R., Palumbo, M., Clementi, S., Bernardini, R., & Cantarella, G. (2009). The CB1/CB2 receptor agonist WIN-55,212-2 reduces viability of human Kaposi's sarcoma cells in vitro. European Journal of Pharmacology, 616(1-3), pp. 16-21. doi:10.1016/j.ejphar.2009.06.004.
    Luca T, et al. The CB1/CB2 Receptor Agonist WIN-55,212-2 Reduces Viability of Human Kaposi's Sarcoma Cells in Vitro. Eur J Pharmacol. 2009 Aug 15;616(1-3):16-21. PubMed PMID: 19539619.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The CB1/CB2 receptor agonist WIN-55,212-2 reduces viability of human Kaposi's sarcoma cells in vitro. AU - Luca,Tonia, AU - Di Benedetto,Giulia, AU - Scuderi,Mariagrazia Rita, AU - Palumbo,Marco, AU - Clementi,Silvia, AU - Bernardini,Renato, AU - Cantarella,Giuseppina, Y1 - 2009/06/17/ PY - 2008/12/10/received PY - 2009/05/19/revised PY - 2009/06/03/accepted PY - 2009/6/23/entrez PY - 2009/6/23/pubmed PY - 2009/10/20/medline SP - 16 EP - 21 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 616 IS - 1-3 N2 - Kaposi's sarcoma is a highly vascularized mesenchymal neoplasm arising with multiple lesions of the skin. Endogenous cannabinoids have been shown to inhibit proliferation of a wide spectrum of tumor cells. We studied the effects of cannabinoids on human Kaposi's sarcoma cell proliferation in vitro. To do so, we first investigated the presence of the cannabinoid receptors CB(1) and CB(2) mRNAs in the human Kaposi's sarcoma cell line KS-IMM by RT-PCR and, subsequently, the effects of the mixed CB(1)/CB(2) agonist WIN-55,212-2 (WIN) on cell proliferation in vitro. WIN showed antimitogenic effects on Kaposi's sarcoma cells. Western blot analysis of Kaposi's sarcoma lysates suggested that WIN treatment induced activation of both caspase-3 and -6, as well as increased phosphorylation of the stress kinase p38 and JNK, along with transient phosphorylation of ERK(1/2). To better characterize the involvement of each single CB receptor in cannabinoid-induced cell death, we incubated Kaposi's sarcoma cells with different selective cannabinoid receptor agonists, respectively ACEA (CB(1)) and JWH-133 (CB(2)). None of the agonists was able to induce KS-IMM cell apoptosis. Moreover, we co-incubated Kaposi's sarcoma cells with WIN-55,212-2 and either the CB(1) receptor antagonist AM251, the CB(2) receptor antagonist AM630, or a combination of both substances. The CB(2) receptor antagonist AM630 was able to significantly increase survival of Kaposi's sarcoma cells treated with WIN. In view of the antiproliferative effects of cannabinoids on KS-IMM cells, one could envision the cannabinoid system as a potential target for pharmacological treatment of Kaposi's sarcoma. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/19539619/The_CB1/CB2_receptor_agonist_WIN_55212_2_reduces_viability_of_human_Kaposi's_sarcoma_cells_in_vitro_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(09)00515-9 DB - PRIME DP - Unbound Medicine ER -